Intercellular adhesion molecule-1 is required for chemoattractant-induced leukocyte adhesion in resting, but not inflamed, venules in vivo

The leukocyte integrins LFA-1 and Mac-1 bind to endothelial intercellular a dhesion molecule-1 (ICAM-1). Leukocyte adhesion induced by micropipette inj ection of formylmethionylleucylphenylalanine (fMLP) or macrophage inflammat ory protein 2 (MIP-2) next to a venule in the exteriorized mouse cremaster muscle was almost completely blocked after intravenous injection of the ICA M-1 mAb YN-1. In contrast, after 2-h pretreatment with TNF-alpha, leukocyte adhesion induced in postcapillary venules by fMLP or MIP-2 was not blocked by the ICAM-1 mAb. Leukocyte adhesion was significantly reduced by mAb GAM E-46 to CD18 even after TNF-alpha treatment. We conclude that ICAM-1 is nec essary for neutrophil adhesion to unstimulated endothelium, but not for adh esion to cytokine-stimulated endothelium. Although ICAM-1 is expressed at h igh levels after TNF-alpha, ICAM-1 either is not functional or is redundant with other endothelial ligands for beta (2), integrins. (C) 2000 Academic Press.